101 research outputs found
Advances in understanding ischemic acute kidney injury
Acute kidney injury (AKI) is independently associated with increased morbidity and mortality. Ischemia is the leading cause of AKI, and short of supportive measures, no currently available therapy can effectively treat or prevent ischemic AKI. This paper discusses recent developments in the understanding of ischemic AKI pathophysiology, the emerging relationship between ischemic AKI and development of progressive chronic kidney disease, and promising novel therapies currently under investigation. On the basis of recent breakthroughs in understanding the pathophysiology of ischemic AKI, therapies that can treat or even prevent ischemic AKI may become a reality in the near future
Optically levitated nanoparticle as a model system for stochastic bistable dynamics
Nano-mechanical resonators have gained an increasing importance in nanotechnology owing to their contributions to both fundamental and applied science. Yet, their small dimensions and mass raises some challenges as their dynamics gets dominated by nonlinearities that degrade their performance, for instance in sensing applications. Here, we report on the precise control of the nonlinear and stochastic bistable dynamics of a levitated nanoparticle in high vacuum. We demonstrate how it can lead to efficient signal amplification schemes, including stochastic resonance. This work contributes to showing the use of levitated nanoparticles as a model system for stochastic bistable dynamics, with applications to a wide variety of fields.inancial support from the ERC- QnanoMECA (Grant No. 64790), the Spanish Ministry of Economy and Competitiveness, under grant FIS2016-80293-R and through the âSevero Ochoaâ Programme for Centres of Excellence in R&D (SEV-2015-0522), FundaciĂł Privada CELLEX and from the CERCA Programme/Generalitat de Catalunya. J.G. has been supported by H2020-MSCA-IF-2014 under REA grant Agreement No. 655369. L.R. acknowledges support from an ETH Marie Curie Cofund Fellowship
Frequency fluctuations in silicon nanoresonators
Frequency stability is key to performance of nanoresonators. This stability
is thought to reach a limit with the resonator's ability to resolve
thermally-induced vibrations. Although measurements and predictions of
resonator stability usually disregard fluctuations in the mechanical frequency
response, these fluctuations have recently attracted considerable theoretical
interest. However, their existence is very difficult to demonstrate
experimentally. Here, through a literature review, we show that all studies of
frequency stability report values several orders of magnitude larger than the
limit imposed by thermomechanical noise. We studied a monocrystalline silicon
nanoresonator at room temperature, and found a similar discrepancy. We propose
a new method to show this was due to the presence of frequency fluctuations, of
unexpected level. The fluctuations were not due to the instrumentation system,
or to any other of the known sources investigated. These results challenge our
current understanding of frequency fluctuations and call for a change in
practices
National Prevalence and Trends of HIV Transmitted Drug Resistance in Mexico
BACKGROUND: Transmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access. METHODOLOGY/PRINCIPAL FINDINGS: We designed a study to assess HIV diversity and transmitted drug resistance (TDR) prevalence and trends in Mexico. 1655 ART-naĂŻve patients from 12 Mexican states were enrolled from 2005 to 2010. TDR was assessed from plasma HIV pol sequences using Stanford scores and the WHO TDR surveillance mutation list. TDR prevalence fluctuations over back-projected dates of infection were tested. HIV subtype B was highly prevalent in Mexico (99.9%). TDR prevalence (Stanford score>15) in the country for the study period was 7.4% (95% CI, 6.2â¶8.8) and 6.8% (95% CI, 5.7â¶8.2) based on the WHO TDR surveillance mutation list. NRTI TDR was the highest (4.2%), followed by NNRTI (2.5%) and PI (1.7%) TDR. Increasing trends for NNRTI (pâ=â0.0456) and PI (pâ=â0.0061) major TDR mutations were observed at the national level. Clustering of viruses containing minor TDR mutations was observed with some apparent transmission pairs and geographical effects. CONCLUSIONS: TDR prevalence in Mexico remains at the intermediate level and is slightly lower than that observed in industrialized countries. Whether regional variations in TDR trends are associated with differences in antiretroviral drug usage/ART efficacy or with local features of viral evolution remains to be further addressed
A Meta-Analysis of Array-CGH Studies Implicates Antiviral Immunity Pathways in the Development of Hepatocellular Carcinoma
BACKGROUND: The development and progression of hepatocellular carcinoma (HCC) is significantly correlated to the accumulation of genomic alterations. Array-based comparative genomic hybridization (array CGH) has been applied to a wide range of tumors including HCCs for the genome-wide high resolution screening of DNA copy number changes. However, the relevant chromosomal variations that play a central role in the development of HCC still are not fully elucidated.
METHODS: In present study, in order to further characterize the copy number alterations (CNAs) important to HCC development, we conducted a meta-analysis of four published independent array-CGH datasets including total 159 samples.
RESULTS: Eighty five significant gains (frequency â„ 25%) were mostly mapped to five broad chromosomal regions including 1q, 6p, 8q, 17q and 20p, as well as two narrow regions 5p15.33 and 9q34.2-34.3. Eighty eight significant losses (frequency â„ 25%) were most frequently present in 4q, 6q, 8p, 9p, 13q, 14q, 16q, and 17p. Significant correlations existed between chromosomal aberrations either located on the same chromosome or the different chromosomes. HCCs with different etiologies largely exhibited surprisingly similar profiles of chromosomal aberrations with only a few exceptions. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the genes affected by these chromosomal aberrations were significantly enriched in 31 canonical pathways with the highest enrichment observed for antiviral immunity pathways.
CONCLUSIONS: Taken together, our findings provide novel and important clues for the implications of antiviral immunity-related gene pathways in the pathogenesis and progression of HCC
DLK1 Is a Somato-Dendritic Protein Expressed in Hypothalamic Arginine-Vasopressin and Oxytocin Neurons
Delta-Like 1 Homolog, Dlk1, is a paternally imprinted gene encoding a transmembrane protein involved in the differentiation of several cell types. After birth, Dlk1 expression decreases substantially in all tissues except endocrine glands. Dlk1 deletion in mice results in pre-natal and post-natal growth deficiency, mild obesity, facial abnormalities, and abnormal skeletal development, suggesting involvement of Dlk1 in perinatal survival, normal growth and homeostasis of fat deposition. A neuroendocrine function has also been suggested for DLK1 but never characterised. To evaluate the neuroendocrine function of DLK1, we first characterised Dlk1 expression in mouse hypothalamus and then studied post-natal variations of the hypothalamic expression. Western Blot analysis of adult mouse hypothalamus protein extracts showed that Dlk1 was expressed almost exclusively as a soluble protein produced by cleavage of the extracellular domain. Immunohistochemistry showed neuronal DLK1 expression in the suprachiasmatic (SCN), supraoptic (SON), paraventricular (PVN), arcuate (ARC), dorsomedial (DMN) and lateral hypothalamic (LH) nuclei. DLK1 was expressed in the dendrites and perikarya of arginine-vasopressin neurons in PVN, SCN and SON and in oxytocin neurons in PVN and SON. These findings suggest a role for DLK1 in the post-natal development of hypothalamic functions, most notably those regulated by the arginine-vasopressin and oxytocin systems
A self-stabilized coherent phonon source driven by optical forces
[EN] We report a novel injection scheme that allows for phonon lasing in a one-dimensional optomechanical photonic crystal, in a sideband unresolved regime and with cooperativity values as low as 10-2. It extracts energy from a cw infrared laser source and is based on the triggering of a thermooptical/free-carrier-dispersion self-pulsing limit-cycle, which anharmonically modulates the radiation pressure force. The large amplitude of the coherent mechanical motion acts as a feedback that stabilizes and entrains the self-pulsing oscillations to simple fractions of the mechanical frequency. A manifold of frequency-entrained regions with two different mechanical modes (at 54 and 122 MHz) are observed as a result of the wide tuneability of the natural frequency of the self-pulsing. The system operates at ambient conditions of pressure and temperature in a silicon platform, which enables its exploitation in sensing, intra-chip metrology or time-keeping applications.This work was supported by the European Comission project TAILPHOX (ICT-FP7-233883), the ERC Advanced Grant SOULMAN (ERC-FP7-321122) and the Spanish MINECO project TAPHOR (MAT2012-31392). The authors sincerely thank B. Djafari-Rouhani, Y. Pennec and M. Oudich for the design of the OM photonic crystal, A. Trifonova, S. Valenzuela and E. Weig for a critical reading of the manuscript and A. Tredicucci for fruitful discussions. A. M and A. G thank L. Bellieres and N. Sanchez-Losilla for their contributions in the OM photonic crystal etching processes. DNU and JGB gratefully acknowledge the support of a Beatriu de Pinos and a Juan de la Cierva postdoctoral fellowship, respectively.Navarro UrrĂos, D.; Capuj, NE.; Gomis-Bresco, J.; Alzina, F.; Pitanti, A.; Griol Barres, A.; MartĂnez Abietar, AJ.... (2015). A self-stabilized coherent phonon source driven by optical forces. Scientific Reports. 5(15733):1-7. https://doi.org/10.1038/srep15733S17515733Feng, X. L., White, C. J., Hajimiri, A. & Roukes, M. L. A self-sustaining ultrahigh-frequency nanoelectromechanical oscillator. Nat. Nanotech. 3, 342 (2008).Aspelmeyer, M., Kippenberg, T. J. & Marquardt, F. Cavity optomechanics. Rev. Mod. Phys. 86, 1391 (2014).Pikovsky, A., Rosenblum, M. & Kurths, J. Synchronization: a universal concept in nonlinear sciences (Cambridge university press, Cambridge 2003).Heinrich, G., Ludwig, M., Qian, J., Kubala, B. & Marquardt, F. Collective dynamics in optomechanical arrays. Phys. Rev. Lett. 107, 043603 (2011).Zhang, M. et al. Synchronization of micromechanical oscillators using light. Phys. Rev. Lett. 109, 233906 (2012).Bagheri, M., Poot, M., Fan, L., Marquardt, F. & Tang, H. X. Photonic cavity synchronization of nanomechanical oscillators. Phys. Rev. Lett. 111, 213902 (2013).Matheny, M. H. et al. Phase synchronization of two anharmonic nanomechanical oscillators. Phys. Rev. Lett. 112, 014101 (2014).Mahboob, I., Nishiguchi, K., Fujiwara, A. & Yamaguchi, H. Phonon Lasing in an Electromechanical Resonator. Phys. Rev. Lett. 110, 127202 (2013).Grudinin, I. S., Lee, H., Painter, O. & Vahala, K. J. Phonon laser action in a tunable two-level system. Phys. Rev. Lett. 104, 083901 (2010).Kippenberg, T. J., Rokhsari, H., Carmon, T., Scherer, A. & Vahala, K. J. Analysis of radiation-pressure induced mechanical oscillation of an optical microcavity. Phys. Rev. Lett. 95, 033901 (2005).Kippenberg, T. J. & Vahala, K. J. Cavity optomechanics: back-action at the mesoscale. Science 321, 1172â1176 (2008).Schliesser, A. & Kippenberg, T. J. in Cavity Optomechanics, Aspelmeyer M., Kippenberg T. J. & Marquardt F. Eds (Springer: Berlin Heidelberg, 2014), chap. 6.Roels, J. et al. Parametric instability of an integrated micromechanical oscillator by means of active optomechanical feedback. Opt. Express 19, 13081â13088 (2011).Villanueva, L. G. et al. A nanoscale parametric feedback oscillator. Nano Lett. 11, 5054â5059 (2011).Gomis-Bresco, J. et al. A one-dimensional optomechanical crystal with a complete phononic band gap. Nat. Commun. 5, 4452 (2014).Barclay, P. E., Srinivasan, K. & Painter, O. Nonlinear response of silicon photonic crystal microresonators excited via an integrated waveguide and fiber taper. Opt. Express 13, 801 (2005).Johnson, S. G. et al. Perturbation theory for Maxwellâs equations with shifting material boundaries. Phys. Rev. E 65, 066611 (2003).Chen, S., Zhang, L., Fei, Y. & Cao, T. Bistability and self-pulsation phenomena in silicon microring resonators based on nonlinear optical effects. Opt. Express 20, 7454 (2012).Armaroli, A. et al. Oscillatory dynamics in nanocavities with noninstantaneous Kerr response. Phys. Rev. A 84, 053816 (2011).Mancinelli, M., Borghi, M., Ramiro-Manzano, F., Fedeli, J. M. & Pavesi, L. Chaotic dynamics in coupled resonator sequences. Opt. Express 22, 14505 (2014).Xu, Q. & Lipson, M. Carrier-induced optical bistability in silicon ring resonators. Opt. Lett. 31, 341 (2006).Johnson, T. J., Borselli, M. & Painter, O. Self-induced optical modulation of the transmission through a high-Q silicon microdisk resonator. Opt. Express, 14, 817â831 (2006).Pernice, W. H., Li, M. & Tang, H. X. Time-domain measurement of optical transport in silicon micro-ring resonators. Opt. Express, 18, 18438â18452 (2010).Yang, J. et al. Radio frequency regenerative oscillations in monolithic high-Q/V heterostructured photonic crystal cavities. Appl. Phys. Lett. 104, 061104 (2014).Zhang, L., Fei, Y., Cao, Y., Lei, X. & Chen, S. Experimental observations of thermo-optical bistability and self-pulsation in silicon microring resonators. JOSA B 31, 201â206 (2014).Deng, Y., Liu, F., Leseman, Z. & Hossein-Zadeh, M. Thermo-optomechanical oscillator for sensing applications. Opt. Express 21, 4653â4664 (2013).Lifshitz, R. & Cross, M. C. Response of parametrically driven nonlinear coupled oscillators with application to micromechanical and nanomechanical resonator arrays. Phys. Rev. B 67, 134302 (2003)
Silicon particles as trojan horses for potential cancer therapy
[EN] Background: Porous silicon particles (PSiPs) have been used extensively as drug delivery systems, loaded with chemical species for disease treatment. It is well known from silicon producers that silicon is characterized by a low reduction potential, which in the case of PSiPs promotes explosive oxidation reactions with energy yields exceeding that of trinitrotoluene (TNT). The functionalization of the silica layer with sugars prevents its solubilization, while further functionalization with an appropriate antibody enables increased bioaccumulation inside selected cells. Results: We present here an immunotherapy approach for potential cancer treatment. Our platform comprises the use of engineered silicon particles conjugated with a selective antibody. The conceptual advantage of our system is that after reaction, the particles are degraded into soluble and excretable biocomponents. Conclusions: In our study, we demonstrate in particular, specific targeting and destruction of cancer cells in vitro. The fact that the LD50 value of PSiPs-HER-2 for tumor cells was 15-fold lower than the LD50 value for control cells demonstrates very high in vitro specificity. This is the first important step on a long road towards the design and development of novel chemotherapeutic agents against cancer in general, and breast cancer in particular.The authors acknowledge financial support from the following projects FIS2009-07812, MAT2012-35040, PROMETEO/2010/043, CTQ2011-23167, CrossSERS, FP7 MC-IEF 329131, and HSFP (project RGP0052/2012) and Medcom Tech SA. Xiang Yu acknowledges support by the Chinese government (CSC, Nr. 2010691036).Fenollosa Esteve, R.; Garcia-Rico, E.; Alvarez, S.; Alvarez, R.; Yu, X.; Rodriguez, I.; Carregal-Romero, S.... (2014). Silicon particles as trojan horses for potential cancer therapy. 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Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a life-saving procedure used for the treatment of selected hematological malignancies, inborn errors of metabolism, and bone marrow failures. The role of neutrophils in alloHSCT has been traditionally evaluated only in the context of their ability to act as a first line of defense against infection. However, recent evidence has highlighted neutrophils as key effectors of innate and adaptive immune responses through a wide array of newly discovered functions. Accordingly, neutrophils are emerging as highly versatile cells that are able to acquire different, often opposite, functional capacities depending on the microenvironment and their differentiation status. Herein, we review the current knowledge on the multiple functions that neutrophils exhibit through the different stages of alloHSCT, from the hematopoietic stem cell (HSC) mobilization in the donor to the immunological reconstitution that occurs in the recipient following HSC infusion. We also discuss the influence exerted on neutrophils by the immunosuppressive drugs delivered in the course of alloHSCT as part of graft-versus-host disease (GVHD) prophylaxis. Finally, the potential involvement of neutrophils in alloHSCT-related complications, such as transplant-associated thrombotic microangiopathy (TA-TMA), acute and chronic GVHD, and cytomegalovirus (CMV) reactivation, is also discussed. Based on the data reviewed herein, the role played by neutrophils in alloHSCT is far greater than a simple antimicrobial role. However, much remains to be investigated in terms of the potential functions that neutrophils might exert during a highly complex procedure such as alloHSCT
Global patterns and drivers of ecosystem functioning in rivers and riparian zones
River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.peerReviewe
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